title: A retrospective review of metronidazole and vancomycin in the management of Clostridium difficile infection in patients with hematologic malignancies.
abstract: BACKGROUND
  The incidence and severity of Clostridium difficile infection has significantly increased over the past decade. Although the epidemiology and treatment of C. difficile infection is well elucidated in the non-oncology population, it is poorly understood among cancer patients. This illustrates great concern as the majority of these patients are immunosuppressed, which puts them at higher risk for developing severe disease. Furthermore, suboptimal treatment of C. difficile infection can compromise care of underlying malignancy. Due to limited amount of data, we conducted this study to better ascertain the epidemiology and treatment outcomes of C. difficile infection in a subset of oncology patients at our institution.
  
  
  OBJECTIVE
  The primary objective was to assess the incidence and severity of C. difficile infection in patients with hematologic malignancies, including those undergoing hematopoietic stem cell transplant for a hematologic condition. The secondary objectives were to assess: (a) the outcome of C. difficile infection after therapy with metronidazole and/or vancomycin and (b) mortality following C. difficile infection.
  
  
  METHODS
  We performed a retrospective study to assess the incidence and severity of C. difficile infection and to evaluate outcomes of therapy with metronidazole and/or vancomycin among adult patients admitted to the Malignant Hematology/Blood and Marrow Transplantation service at our center from January 2009 to 2012.
  
  
  RESULTS
  Of the 390 admitted patients during the 3-year study period, the overall incidence of C. difficile infection was 18.7% (n = 73). Forty-six patients (63.0%) were deemed to have mild-moderate C. difficile infection. With regards to outcome of therapy, less exposure to antimicrobial agents was significantly associated with a higher resolution rate (p = 0.0029). Response rates to metronidazole were 53.7%, vancomycin 50%, and combination therapy 38.5%, although no difference in achievement of resolution was found among the three treatment modalities (p = 0.5533). Older patients were more likely to experience recurrent C. difficile infection (p = 0.0007). It was found that 55 patients (75.3%) were alive at 6 months.
  
  
  CONCLUSIONS
  These results highlight the high incidence of C. difficile infection in a subset of cancer patients at our institution. Although most patients presented with mild-moderate disease, severity of C. difficile infection in cancer patients may be underestimated due to the frequent presence of neutropenia. This study is the first analysis conducted, which directly compares outcomes of C. difficile infection after therapy with metronidazole, vancomycin, or combination therapy exclusively in patients with hematologic malignancies, including those undergoing hematopoietic stem cell transplant for a hematologic condition. We found no difference in treatment outcomes among metronidazole, vancomycin, or combination therapy. The recommendation from the literature to use metronidazole as the initial drug of choice for mild-moderate C. difficile infection is a reasonable option, although the rate of cure is low. This study highlights the critical need for better treatment options, due to suboptimal response rates to current therapy. Larger scale studies are needed to better understand the epidemiology and management of C. difficile infection in this patient population.
authors.affiliation: Department of Pharmacy, Stony Brook University Hospital, Stony Brook, NY, USA.
authors.forename: Sapna R
authors.initials: SR
authors.lastname: Parmar
authors.forename: Valkal
authors.initials: V
authors.lastname: Bhatt
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Schuster
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016360:Clostridioides difficile; D023381:Endpoint Determination; D004761:Enterocolitis, Pseudomembranous / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D015994:Incidence; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; D014640:Vancomycin
keywords: Clostridium difficile infection; hematologic malignancy; metronidazole; vancomycin